A Vector-Based Short Hairpin RNA Targeting Aurora B Suppresses Human Prostatic Carcinoma Growth

Technol Cancer Res Treat. 2017 Feb;16(1):112-119. doi: 10.1177/1533034616673534. Epub 2016 Oct 17.

Abstract

Aurora kinase B, playing a vital, important role in mitosis, is frequently detected to be overexpressed in many cancer cell lines and various tumor tissues, including prostatic carcinoma. Given the essential function of Aurora kinase B in mitosis and its association with tumorigenesis, it might be a drug target for prostatic carcinoma treatment. In our study, short hairpin RNA targeting Aurora kinase B was cloned into a pGPU6 plasmid vector and then transfected into human prostatic carcinoma cells. The expression level of Aurora kinase B was verified by reverse transcription-polymerase chain reaction and Western blot. At the same time, cell apoptosis was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, fluorescent staining, and flow cytometric analysis. Furthermore, prostate carcinoma cells were injected into mice to establish a tumor xenograft model. Previous studies have shown the effect of pGPU6-shAURKB plasmid on tumor growth in a prostate carcinoma xenogenic implantation model. From the study, we knew that the Aurora kinase B was significantly downregulated in prostate carcinoma cells, and cell apoptosis was also detected higher in treated groups than that in control groups. Moreover, in the prostate carcinoma xenogenic implantation model, compared with the control groups, the tumor growth was inhibited about 78.7% in the pGPU6-shAURKB plasmid-treated group, and cell apoptosis in the experimental group was notably higher than that in control groups. The average duration of tumor-bearing mice was prolonged to about 35 days. The results of experiment indicated that specific knockdown of Aurora kinase B led to prostate carcinoma cells apoptosis and inhibited tumor growth. Our data clearly confirmed that specific knockdown of Aurora kinase B expression by vector-based short hairpin RNA/liposome may be a potential new approach to treat human prostatic carcinoma.

Keywords: Aurora B; RNA interference; cell apoptosis; gene therapy; prostatic carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Aurora Kinase B / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Gene Expression
  • Gene Knockdown Techniques
  • Genetic Vectors / genetics*
  • Humans
  • Male
  • Mice
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • RNA Interference*
  • RNA, Small Interfering / genetics*
  • Transfection
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • RNA, Small Interfering
  • Aurora Kinase B